Telomeric and other guanine-rich DNAs can form a variety of novel four-stranded structures containing G--G base pairs that are stabilized by physiologically important cations such as Na.sup.+ and K.sup.+. See, e.g., E. Henderson, et al., Cell 51, 899-908 (1987); Y. Oka and C. A. Thomas, Nucleic Acids Res. 15, 8877-8898 (1987); D. Sen and W. Gilbert, Nature 334, 364-366 (1988). A number of quadruplex conformational variants have been described and several biological and biotechnological roles have been suggested, including telomere-telomere interactions, telomerase inhibition, chromatin condensation, aptamer structure, mitotic and meiotic chromosomal pairing, promotion of recombination, eukaryotic intron RNA recognition, and repression of eukaryotic transcription and viral replication. See. e.g., E. Henderson et al., supra; M. K. Raghuraman and T. R. Cech, Nucleic Acids Res. 18, 4543-4552 (1990); E. H. Blackburn, J. Biol. Chem. 265, 5919-5921 (1990); D. E. Huizenga and J. W. Szostak, Biochemistry 34, 656-665 (1995); R. F. Macaya et al., Proc. Natl. Acad. Sci. USA 90, 3745-3749 (1993); A. T. Pluta and V. A. Zakian, Nature 337, 429-33 (1989); N. Abdul-Manan, et al., Biochemistry 35, 3545-3554 (1996).
In vitro studies of a consensus SPl transcription factor binding sequence motif oligonucleotide, d(CGC G.sub.4 GCG) (abbreviated G.sub.4 -DNA, SEQ ID NO:1), have shown that four of these oligonucleotides form a parallel intramolecular quadruplex at moderate ionic strengths. See, C. C. Hardin et al., Biochemistry 32, 5870-5880 (1993); D. R. Goodlet et al., Biol. Mass. Spec. 22, 181-183 (1993). Circular dichroism and NMR studies have shown that this quadruplex is inherently stable (T.sub.m of ca. 90.degree. C.) when formed in 20 mM K.sup.+. The biological roles of such a stable complex are clearly worthy of probing, yet definitive detection of these structures in vivo has heretofore not been accomplished.
Several studies have demonstrated the utility of antibodies in elucidating structural features of native and modified nucleic acids. See C. C. Hardin et al., Biochemistry 27, 4169-4177 (1988). Right- and left-handed RNAs and DNAs and triplex DNAs have been studied in vitro and in vivo using polyclonal and monoclonal antibodies. Id.; see also E. M. Lafer et al., Proc. Natl. Acad. Sci. USA 78, 3546-3550 (1981); C. C. Hardin et al., Biochemistry 26, 5191-5199 (1987). Anti-DNA antibodies have been obtained from murine models of systemic lupus erythematosus (SLE). Specifically, (NZB/NZW)F.sub.1 and MRL/Mp-lpr/lpr mice have been shown to produce antibodies that are specific for single- and double-stranded DNA, Z-DNA, RNA and rRNA. See, e.g., C. Andrzejewski et al., J. Immunol. 124, 1499-1502 (1980); M. Herrmann et al., Eur. J. Immunol. 25, 1897-1904 (1995). However, the production of antibodies useful in detecting and characterizing quadruplex nucleic acids has heretofore proved elusive. Accordingly, there exists a need for means and methods to easily detect and study quadruplex nucleic acids, in order to further elucidate the biological functions related thereto.